This trial has been designed to test the hypothesis that nearly normalized glycemia in type I diabetic kidney recipients prevents the diabetic vascular lesions developing in the allografts 2 to 5 years after transplantation into diabetics. Volunteers undergo a needle biopsy of the graft at transplant time, and randomized to stringent or standard glucose control, monitored intensively for 5 years and are biopsied again at 2 and 5 years after transplant. The renal tissue is studied by light and electron microscopy for basement membrane thickening, arterial hyalinosis and mesangial expansion. The latter lesion is the primary endpoint because it correlates with clinical diabetic nephropathy (proteinuria, increased creatinine). Sequential analysis is done every 6 months. Since the patients studied have constituted an inception cohort for diabetic renal disease (all patients at stage zero of nephropathy at the time of onset of the study), this has been a Primary Intervention Trial. In addition to continuing the ongoing Primary Intervention, as recommended by a recent NIH site visit (see text and Appendix), we propose here to start a Follow-up Study. In this study we would test the hypothesis that stringent control initiated 5 years after transplantation will reverse the lesions extant in the graft. In the Follow-up Study we will invite the patients who have completed 5 years of standard treatment, to cross over to maximized treatment and continue for 5 more years in the study with biopsies at 7 and 10 years after transplant. Patients who had baseline biopsies 5 years ago, but declined to join the study, will be re-invited to join the stringent control group after having a 5 year biopsy. Thus far, 97 patients (45 standard, 52 maximized) have been randomized during the 5 year Primary Trail. Thirty-three 5 year biopsies have been obtained. The difference in metabolic control between the two groups has been consistently and statistically significant. The results from the sequential analysis, comparing the two patient groups for histological endpoints are kept confidential and are available to the NIH separately if desired. Considering the important impact of diabetic complications as a pubic health problem and the present ignorance of their causes, we feel our studied - both the Primary Trial and Follow-up Study - are important and must be pursued.